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https://www.readbyqxmd.com/read/29751197/investigating-cytochrome-p450-specificity-during-glycopeptide-antibiotic-biosynthesis-through-a-homologue-hybridization-approach
#1
Clara Brieke, Miroslaw Tarnawski, Anja Greule, Max J Cryle
Cytochrome P450 enzymes perform an impressive range of oxidation reactions against diverse substrate scaffolds whilst generally maintaining a conserved tertiary structure and active site chemistry. Within secondary metabolism, P450 enzymes play widespread and important roles in performing crucial modifications of precursor molecules, with one example of the importance of such reactions being found in the biosynthesis of the glycopeptide antibiotics (GPAs). In GPA biosynthesis P450s, known as Oxy enzymes, are key players in the cyclization of the linear GPA peptide precursor, which is a process that is both essential for their antibiotic activity and is the source of the synthetic challenge of these important antibiotics...
May 3, 2018: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/29719204/drug-drug-interactions-in-the-treatment-for-alcohol-use-disorders-a-comprehensive-review
#2
REVIEW
Guerzoni Simona, Pellesi Lanfranco, Pini Luigi Alberto, Caputo Fabio
Drug interactions are one of the most common causes of side effects in polypharmacy. Alcoholics are a category of patients at high risk of pharmacological interactions, due to the presence of comorbidities, the concomitant intake of several medications and the pharmacokinetic and pharmacodynamic interferences of ethanol. However, the data available on this issue are limited. These reasons often frighten clinicians when prescribing appropriate pharmacological therapies for alcohol use disorder (AUD), where less than 15% of patients receive an appropriate treatment in the most severe forms...
April 29, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29697176/in-vitro-reconstitution-of-oxyc-activity-enables-total-chemo-enzymatic-syntheses-of-vancomycin-aglycone-variants
#3
Clarissa C Forneris, Mohammad R Seyedsayamdost
Since its discovery in 1953, vancomycin has been one of our most important antibiotics in the fight against infectious disease. The bioactivity of vancomycin is potentiated by unusual structural features, including three aromatic crosslinks, the biosynthesis of which has been an active area of investigation for two decades. Two cytochrome P450 enzymes, OxyB and OxyA, have been shown to introduce bisaryl ether linkages with the help of a so-called X-domain. The final crosslink, however, a biaryl bond thought to be installed by OxyC, has remained elusive...
April 26, 2018: Angewandte Chemie
https://www.readbyqxmd.com/read/29690001/erpetogomphus-oxybelis-sp-nov-from-veracruz-mexico-odonata-gomphidae
#4
HÉctor Ortega-Salas
Erpetogomphus oxybelis sp. nov. is described and figured from Río Hondo, Veracruz State, Mexico (18.387 N, -96.174 W, 20 m a.s.l.), the holotype is deposited in the Frost Entomological Museum at Pennsylvania State University, USA [PSUC]. Relationship with members of the ophibolus group sensu Garrison are discussed.
February 11, 2018: Zootaxa
https://www.readbyqxmd.com/read/29664059/excessive-daytime-sleepiness-in-parkinson-s-disease-clinical-implications-and-management
#5
REVIEW
Yun Shen, Jun-Ying Huang, Jie Li, Chun-Feng Liu
Objective: Excessive daytime sleepiness (EDS) is one of the most common sleep abnormalities in patients with Parkinson's disease (PD), yet its multifactorial etiology complicates its treatment. This review summarized recent studies on the epidemiology, etiology, clinical implications, associated features, and evaluation of EDS in PD. The efficacy of pharmacologic and non-pharmacologic treatments for EDS in PD was also reviewed. Data Sources: English language articles indexed in PubMed and Cochrane databases and Chinese-language papers indexed in Wanfang and National Knowledge Infrastructure databases that were published between January 1987 and November 2017 were located using the following search terms: "sleepiness", "sleep and Parkinson's disease", and "Parkinson's disease and treatment"...
April 20, 2018: Chinese Medical Journal
https://www.readbyqxmd.com/read/29522206/in-field-assessment-of-sodium-oxybate-effect-in-pediatric-type-1-narcolepsy-an-actigraphic-study
#6
Marco Filardi, Fabio Pizza, Elena Antelmi, Raffaele Ferri, Vincenzo Natale, Giuseppe Plazzi
Study Objectives: Sodium oxybate (SXB) is a GABAergic agent widely used as off-label treatment in pediatric type 1 narcolepsy (NT1). Here we aimed at analyzing by wrist actigraphy the sleep/wake profile of NT1 children and adolescents in drug-naïve condition and after 1 year of SXB treatment. As secondary aim, we investigated changes on sleepiness, cataplexy and children's anthropometric profile after 1 year of SXB treatment. Methods: Twenty-four drug-naïve NT1 children underwent seven days of actigraphy during the school week...
March 7, 2018: Sleep
https://www.readbyqxmd.com/read/29512449/sodium-oxybate-treatment-in-pediatric-type-1-narcolepsy
#7
Monica Moresco, Fabio Pizza, Elena Antelmi, Giuseppe Plazzi
Narcolepsy type 1 (NT1) is a rare chronic neurologic disorder characterized by excessive daytime sleepiness, cataplexy, sleep paralysis, hallucinations and disrupted nocturnal sleep, usually with onset during childhood/adolescence. Pediatric NT1 is associated with limitations on children's activities and achievements, especially poor performance at school, difficulty with peers due to disease symptoms and comorbidities including depression, obesity, and precocious puberty. NT1 disease is caused by the selective loss of hypocretin-producing neurons in the lateral hypothalamus, most probably related to an autoimmune pathophysiology...
March 5, 2018: Current Drug Metabolism
https://www.readbyqxmd.com/read/29504180/decreased-body-mass-index-during-treatment-with-sodium-oxybate-in-narcolepsy-type-1
#8
Mink S Schinkelshoek, Isabelle M Smolders, Claire E Donjacour, Wisse P van der Meijden, Erik W van Zwet, Rolf Fronczek, Gert Jan Lammers
Narcolepsy type 1 is characterised by an increase in body weight after disease onset, frequently leading to obesity. It was suggested that this weight gain may be counteracted by treatment with sodium oxybate. We here provide longitudinal body mass index data of patients with narcolepsy type 1 after starting treatment with sodium oxybate, compared with patients in whom treatment with modafinil was initiated. Eighty-one individuals with narcolepsy type 1 fulfilled the entry criteria for this retrospective study: 59 had newly started treatment with sodium oxybate and 22 had newly started modafinil...
March 4, 2018: Journal of Sleep Research
https://www.readbyqxmd.com/read/29250981/update-on-treatment-for-idiopathic-hypersomnia
#9
REVIEW
Elisa Evangelista, Régis Lopez, Yves Dauvilliers
Idiopathic hypersomnia (IH) is a poorly characterized orphan central disorder of hypersomnolence responsible for excessive daytime sleepiness (EDS), prolonged nighttime sleep and sleep inertia that often require long-term symptomatic stimulant medication. To date, no drug has currently the authorization for the treatment of IH patients worldwide. Areas covered: The authors reviewed data on pharmacological treatment of IH obtained from published literature (Medline/PubMed/Web of Science) and Clinicaltrial.gov database from 1997 to 2017...
February 2018: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/29221779/effect-of-sodium-oxybate-modafinil-and-their-combination-on-disrupted-nighttime-sleep-in-narcolepsy
#10
Yves Dauvilliers, Thomas Roth, Diane Guinta, Sarah Alvarez-Horine, Efim Dynin, Jed Black
OBJECTIVE: To assess the effects of three narcolepsy treatment modalities on sleep stage shifts associated with disrupted nighttime sleep (DNS) using data from a clinical trial. METHODS: Polysomnograms were reviewed from 155 patients (who had these data available at baseline and 8 weeks) of the 278 patients who were randomized to placebo, 9-g sodium oxybate (SXB)/nightly, 200-600 mg/d modafinil, or SXB + modafinil. Major outcomes of these post hoc analyses, analyzed using analysis of covariance, were change from baseline in number of shifts from Stages N2/3/rapid eye movement (REM) to Stage N1/Wake, and from Stage N1/Wake to REM...
December 2017: Sleep Medicine
https://www.readbyqxmd.com/read/29220873/effect-of-sleep-on-overnight-csf-amyloid-%C3%AE-kinetics
#11
Brendan P Lucey, Terry J Hicks, Jennifer S McLeland, Cristina D Toedebusch, Jill Boyd, Donald L Elbert, Bruce W Patterson, Jack Baty, John C Morris, Vitaliy Ovod, Kwasi G Mawuenyega, Randall J Bateman
Sleep disturbances are associated with future risk of Alzheimer's disease. Disrupted sleep increases soluble amyloid-β, suggesting a mechanism for sleep disturbances to increase Alzheimer's disease risk. We tested this response in humans using indwelling lumbar catheters to serially sample cerebrospinal fluid while participants were sleep-deprived, treated with sodium oxybate, or allowed to sleep normally. All participants were infused with13 C6 -leucine to measure amyloid-β kinetics. We found that sleep deprivation increased overnight amyloid-β-38, amyloid-β-40, and amyloid-β-42 levels by 25-30% via increased overnight amyloid-β production relative to sleeping controls...
December 8, 2017: Annals of Neurology
https://www.readbyqxmd.com/read/29219048/sodium-oxybate-therapy-for-the-treatment-of-alcohol-withdrawal-syndrome-and-the-maintenance-of-alcohol-abstinence
#12
Carmen Mannucci, Simona Pichini, Elvira Ventura Spagnolo, Fabrizio Calapai, Sebastiano Gangemi, Michele Navarra, Gioacchino Calapai
BACKGROUND: Gamma-hydroxybutyrate (GHB or sodium oxybate) is both an exogenous and endogenous molecule with neuromodulator properties. In the United States, GHB is an approved drug for the treatment of narcolepsy and narcolepsy with cataplexy in adults. In some European Union countries, sodium oxybate is applied for the treatment of opioid and alcohol withdrawal. OBJECTIVE: The aim of the present review was to describe the state of art of the pre-clinical research and the clinical evidence related to GHB used alone or in combination with other treatments in alcohol withdrawal syndrome and alcohol abstinence maintenance...
December 7, 2017: Current Drug Metabolism
https://www.readbyqxmd.com/read/29205601/criteria-for-gauging-response-to-sodium-oxybate-for-narcolepsy
#13
Alana D Steffen, Chinglin Lai, Terri E Weaver
Our objective was to define responder criteria using an anchor-based approach for frequency of cataplexy attacks and excessive daytime sleepiness in patients with narcolepsy undergoing sodium oxybate treatment. We used pooled data from two randomized, placebo-controlled, double-blind, multicentre 4- and 8-week trials of sodium oxybate for narcolepsy with cataplexy and analysed using receiver operator characteristics analysis. The percentage change in frequency of weekly cataplexy attacks and the Epworth Sleepiness Scale outcomes were compared with Clinical Global Impression of Change ratings, used as the anchor to define true response...
December 5, 2017: Journal of Sleep Research
https://www.readbyqxmd.com/read/29120249/alcohol-addiction-the-safety-of-available-approved-treatment-options
#14
REVIEW
Mariangela Antonelli, Anna Ferrulli, Luisa Sestito, Gabriele A Vassallo, Claudia Tarli, Carolina Mosoni, Maria M Rando, Antonio Mirijello, Antonio Gasbarrini, Giovanni Addolorato
Alcohol Use Disorders (AUD) is a leading cause of mortality and morbidity worldwide. At present disulfiram, naltrexone and acamprosate are approved for the treatment of AUD in U.S. and Europe. Nalmefene is approved in Europe and sodium oxybate is approved in Italy and Austria only. Baclofen received a 'temporary recommendation for use' in France. Areas covered: The safety of the above mentioned medications on liver, digestive system, kidney function, nervous system, pregnancy and lactation and their possible side effects are described and discussed...
February 2018: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/29114733/sodium-oxybate-for-excessive-daytime-sleepiness-and-sleep-disturbance-in-parkinson-disease-a-randomized-clinical-trial
#15
Fabian Büchele, Marc Hackius, Sebastian R Schreglmann, Wolfgang Omlor, Esther Werth, Angelina Maric, Lukas L Imbach, Stefan Hägele-Link, Daniel Waldvogel, Christian R Baumann
Importance: Sleep-wake disorders are a common and debilitating nonmotor manifestation of Parkinson disease (PD), but treatment options are scarce. Objective: To determine whether nocturnal administration of sodium oxybate, a first-line treatment in narcolepsy, is effective and safe for excessive daytime sleepiness (EDS) and disturbed nighttime sleep in patients with PD. Design, Setting, and Participants: Randomized, double-blind, placebo-controlled, crossover phase 2a study carried out between January 9, 2015, and February 24, 2017...
January 1, 2018: JAMA Neurology
https://www.readbyqxmd.com/read/29108652/psychosis-in-a-22-year-old-woman-with-narcolepsy-after-restarting-sodium-oxybate
#16
Patrick J Buckley, Chelsea T Wolf
No abstract text is available yet for this article.
October 10, 2017: Psychosomatics
https://www.readbyqxmd.com/read/29031763/correlation-between-the-epworth-sleepiness-scale-and-the-maintenance-of-wakefulness-test-in-patients-with-narcolepsy-participating-in-two-clinical-trials-of-sodium-oxybate
#17
RANDOMIZED CONTROLLED TRIAL
Milton Erman, Helene Emsellem, Jed Black, Fannie Mori, Geert Mayer
BACKGROUND: In evaluating pathologic sleepiness, the Epworth Sleepiness Scale (ESS) assesses subjective sleep propensity; the Maintenance of Wakefulness Test (MWT) is an objective measure of the ability to stay awake. This analysis evaluated the strength of the correlation between ESS and MWT with regard to absolute values in scores. METHODS: Data were analyzed separately from the intent-to-treat populations of two eight-week clinical trials of sodium oxybate for the treatment of narcolepsy, SXB-15 and SXB-22...
October 2017: Sleep Medicine
https://www.readbyqxmd.com/read/28919445/cognitive-effects-of-labeled-addictolytic-medications
#18
REVIEW
Camille Noélie Pujol, Cecilia Paasche, Vincent Laprevote, Benoit Trojak, Pierre Vidailhet, Elisabeth Bacon, Laurence Lalanne
INTRODUCTION: Alcohol, tobacco, and illegal drug usage is pervasive throughout the world, and abuse of these substances is a major contributor to the global disease burden. Many pharmacotherapies have been developed over the last 50years to target addictive disorders. While the efficacy of these pharmacotherapies is largely recognized, their cognitive impact is less known. However, all substance abuse disorders are known to promote cognitive disorders like executive dysfunction and memory impairment...
September 14, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28860883/assessing-narcolepsy-with-cataplexy-in-children-and-adolescents-development-of-a-cataplexy-diary-and-the-ess-chad
#19
Y Grace Wang, Khadra Benmedjahed, Jérémy Lambert, Christopher J Evans, Steve Hwang, Jed Black, Murray W Johns
OBJECTIVE: The aim of this study was to qualitatively evaluate concepts for incorporation into a daily diary to capture cataplexy frequency and to assess the content validity of the Epworth Sleepiness Scale for Children and Adolescents (ESS-CHAD) in pediatric patients with narcolepsy. PATIENTS AND METHODS: Face-to-face concept elicitation and cognitive interviews were conducted with children (7-9 years; n=13) and adolescents (10-17 years; n=16) who have narcolepsy with cataplexy, and their parents/caregivers...
2017: Nature and Science of Sleep
https://www.readbyqxmd.com/read/28811136/determination-of-ghb-and-ghb-%C3%AE-o-glucuronide-in-hair-of-three-narcoleptic-patients-comparison-between-single-and-chronic-ghb-exposure
#20
Lena-Maria Mehling, Xin Wang, Sys-Stybe Johansen, Annika Spottke, Anna Heidbreder, Peter Young, Burkhard Madea, Cornelius Hess
Gamma-hydroxybutyric acid (GHB) can be used as a knock-out drug in drug facilitated crime (DFC). Due to its rapid metabolism and resulting narrow detection window, uncovering GHB use in DFC still constitutes a problem. In this experiment we determined the GHB and GHB-β-O-glucuronide (GHB-Gluc) concentrations in hair samples after single and chronic GHB exposures. Hair samples of three narcoleptic patients therapeutically taking sodium oxybate (GHB-sodium-salt) were collected. Patients 1 (P1) and 2 (P2) took the medication for nine and six years, respectively...
September 2017: Forensic Science International
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